This paper is an invited perspective written in association with the awarding of the 2018 American Society of Mechanical Engineers Van C. Mow Medal. Inspired by Professor Mow's collaboration with Professor Michael Lai and the role mathematical modeling played in their work on cartilage biomechanics, this article uses our group's work on myocardial infarct healing as an example of the potential value of models in modern experimental biomechanics. Focusing more on the thought process and lessons learned from our studies on infarct mechanics than on the details of the science, this article argues that the complexity of current research questions and the wealth of information already available about almost any cell, tissue, or organ should change how we approach problems and design experiments. In particular, this paper proposes that constructing a mathematical or computational model is now in many cases a critical prerequisite to designing scientifically useful, informative experiments.

References

References
1.
Mow
,
V. C.
,
Kuei
,
S. C.
,
Lai
,
W. M.
, and
Armstrong
,
C. G.
,
1980
, “
Biphasic Creep and Stress Relaxation of Articular Cartilage in Compression? Theory and Experiments
,”
ASME J. Biomech. Eng.
,
102
(
1
), pp.
73
84
.
2.
Armstrong
,
C. G.
,
Lai
,
W. M.
, and
Mow
,
V. C.
,
1984
, “
An Analysis of the Unconfined Compression of Articular Cartilage
,”
ASME J. Biomech. Eng.
,
106
(
2
), pp.
165
173
.
3.
Lai
,
W. M.
,
Hou
,
J. S.
, and
Mow
,
V. C.
,
1991
, “
A Triphasic Theory for the Swelling and Deformation Behaviors of Articular Cartilage
,”
ASME J. Biomech. Eng.
,
113
(
3
), pp.
245
258
.
4.
Holmes
,
J. W.
,
Nuñez
,
J. A.
, and
Covell
,
J. W.
,
1997
, “
Functional Implications of Myocardial Scar Structure
,”
Am. J. Physiol.
,
272
(
5 Pt 2
), pp.
H2123
H2130
.
5.
Fomovsky
,
G. M.
, and
Holmes
,
J. W.
,
2010
, “
Evolution of Scar Structure, Mechanics, and Ventricular Function After Myocardial Infarction in the Rat
,”
Am. J. Physiol. Heart Circ. Physiol.
,
298
(
1
), pp.
H221
H228
.
6.
Fomovsky
,
G. M.
,
Rouillard
,
A. D.
, and
Holmes
,
J. W.
,
2012
, “
Regional Mechanics Determine Collagen Fiber Structure in Healing Myocardial Infarcts
,”
J. Mol. Cell. Cardiol.
,
52
(
5
), pp.
1083
1090
.
7.
Fomovsky
,
G. M.
,
Macadangdang
,
J. R.
,
Ailawadi
,
G.
, and
Holmes
,
J. W.
,
2011
, “
Model-Based Design of Mechanical Therapies for Myocardial Infarction
,”
J. Cardiovasc. Transl. Res.
,
4
(
1
), pp.
82
91
.
8.
Fomovsky
,
G. M.
,
Clark
,
S. A.
,
Parker
,
K. M.
,
Ailawadi
,
G.
, and
Holmes
,
J. W.
,
2012
, “
Anisotropic Reinforcement of Acute Anteroapical Infarcts Improves Pump Function
,”
Circ. Heart Fail.
,
5
(
4
), pp.
515
522
.
9.
Richardson
,
W. J.
,
Clarke
,
S. A.
,
Quinn
,
T. A.
, and
Holmes
,
J. W.
,
2015
, “
Physiological Implications of Myocardial Scar Structure
,”
Compr. Physiol.
,
5
(
4
), pp.
1877
1909
.
10.
Clarke
,
S. A.
,
Richardson
,
W. J.
, and
Holmes
,
J. W.
,
2016
, “
Modifying the Mechanics of Healing Infarcts: Is Better the Enemy of Good?
,”
J. Mol. Cell. Cardiol.
,
93
, pp.
115
124
.
11.
Holmes
,
J. W.
,
Laksman
,
Z.
, and
Gepstein
,
L.
,
2016
, “
Making Better Scar: Emerging Approaches for Modifying Mechanical and Electrical Properties Following Infarction and Ablation
,”
Prog. Biophys. Mol. Biol.
,
120
(
1–3
), pp.
134
148
.
12.
Holmes
,
J. W.
,
Yamashita
,
H.
,
Waldman
,
L. K.
, and
Covell
,
J. W.
,
1994
, “
Scar Remodeling and Transmural Deformation After Infarction in the Pig
,”
Circulation
,
90
(
1
), pp.
411
420
.
13.
Zimmerman
,
S. D.
,
Karlon
,
W. J.
,
Holmes
,
J. W.
,
Omens
,
J. H.
, and
Covell
,
J. W.
,
2000
, “
Structural and Mechanical Factors Influencing Infarct Scar Collagen Organization
,”
Am. J. Physiol. Heart Circ. Physiol.
,
278
(
1
), pp.
H194
H200
.
14.
Knezevic
,
V.
,
Sim
,
A. J.
,
Borg
,
T. K.
, and
Holmes
,
J. W.
,
2002
, “
Isotonic Biaxial Loading of Fibroblast-Populated Collagen Gels: A Versatile, Low-Cost System for the Study of Mechanobiology
,”
Biomech. Model. Mechanobiol.
,
1
(
1
), pp.
59
67
.
15.
Costa
,
K. D.
,
Lee
,
E. J.
, and
Holmes
,
J. W.
,
2003
, “
Creating Alignment and Anisotropy in Engineered Heart Tissue: Role of Boundary Conditions in a Model Three-Dimensional Culture System
,”
Tissue Eng.
,
9
(
4
), pp.
567
577
.
16.
Thomopoulos
,
S.
,
Fomovsky
,
G. M.
, and
Holmes
,
J. W.
,
2005
, “
The Development of Structural and Mechanical Anisotropy in Fibroblast Populated Collagen Gels
,”
ASME J. Biomech. Eng.
,
127
(
5
), pp.
742
750
.
17.
Thomopoulos
,
S.
,
Fomovsky
,
G. M.
,
Chandran
,
P. L.
, and
Holmes
,
J. W.
,
2007
, “
Collagen Fiber Alignment Does Not Explain Mechanical Anisotropy in Fibroblast Populated Collagen Gels
,”
ASME J. Biomech. Eng.
,
129
(
5
), pp.
642
650
.
18.
Lee
,
E. J.
,
Holmes
,
J. W.
, and
Costa
,
K. D.
,
2008
, “
Remodeling of Engineered Tissue Anisotropy in Response to Altered Loading Conditions
,”
Ann. Biomed. Eng.
,
36
(
8
), pp.
1322
1334
.
19.
Janes
,
K. A.
,
Chandran
,
P. L.
,
Ford
,
R. M.
,
Lazzara
,
M. J.
,
Papin
,
J. A.
,
Peirce
,
S. M.
,
Saucerman
,
J. J.
, and
Lauffenburger
,
D. A.
,
2017
, “
An Engineering Design Approach to Systems Biology
,”
Integr. Biol. (Camb).
,
9
(
7
), pp.
574
583
.
20.
Rouillard
,
A. D.
, and
Holmes
,
J. W.
,
2012
, “
Mechanical Regulation of Fibroblast Migration and Collagen Remodelling in Healing Myocardial Infarcts
,”
J. Physiol.
,
590
(
18
), pp.
4585
4602
.
21.
Caggiano
,
L. R.
,
Lee
,
J.-J.
, and
Holmes
,
J. W.
,
2018
, “
Surgical Reinforcement Alters Collagen Alignment and Turnover in Healing Myocardial Infarcts
,”
Am. J. Physiol. Heart Circ. Physiol.
,
315
(
4
), pp.
H1041
H1050
.
22.
Huxley
,
A. F.
,
1957
, “
Muscle Structure and Theories of Contraction
,”
Prog. Biophys. Biophys. Chem.
,
7
, pp.
255
318
.
23.
Noble
,
D.
,
2002
, “
Modeling the Heart–From Genes to Cells to the Whole Organ
,”
Science
,
295
(
5560
), pp.
1678
1682
.
24.
Aldridge
,
B. B.
,
Burke
,
J. M.
,
Lauffenburger
,
D. A.
, and
Sorger
,
P. K.
,
2006
, “
Physicochemical Modelling of Cell Signalling Pathways
,”
Nat. Cell Biol.
,
8
(
11
), pp.
1195
1203
.
25.
Chuang
,
H.-Y.
,
Hofree
,
M.
, and
Ideker
,
T.
,
2010
, “
A Decade of Systems Biology
,”
Annu. Rev. Cell Dev. Biol.
,
26
, pp.
721
744
.
26.
Ditlev
,
J. A.
,
Mayer
,
B. J.
, and
Loew
,
L. M.
,
2013
, “
There is More Than One Way to Model an Elephant. Experiment-Driven Modeling of the Actin Cytoskeleton
,”
Biophys. J.
,
104
(
3
), pp.
520
532
.
27.
Peck
,
S. L.
,
2004
, “
Simulation as Experiment: A Philosophical Reassessment for Biological Modeling
,”
Trends Ecol. Evol.
,
19
(
10
), pp.
530
534
.
28.
Humphrey
,
J. D.
,
2002
,
Cardiovascular Solid Mechanics: Cells, Tissues, and Organs
,
Springer-Verlag
,
New York
.
You do not currently have access to this content.